DESCRIPTION: (Applicant's Abstract) This is a Research Scientist Award for Dr. Allyn Howlett, who has a B.S. cum laude, in Biochemistry and Ph.D. in Pharmacology and Toxicology. Dr. Howlett is a tenured Professor in the Dept. Pharmacological and Physiological Science at Saint Louis University School of Medicine, a large, technically multidisciplinary department with research interests in cardiovascular, endocrine and neural physiology and pharmacology. Dr. Howlett's research effort is concentrated on the pharmacological, biochemical and cellular regulation of the CB1 cannabinoid receptor. Her intention is to maintain an active research laboratory in which students, fellows and visiting scientists can exchange ideas and share from their areas of expertise. Toward this goal, Dr. Howlett requests the continuation of this RSA in order to allow ample research time to attend to each individual working on the research project and to maintain research collaborations with other scientists. The RSA will also foster continued professional development through research meetings, short courses and communication with other research scientist. Dr. Howlett's research projects have been described in two NIDA-funded R01 grants. "Cannabinoid Receptor Structure-Activity Releationships" examines the receptor-ligand interaction (cannabinoid, aminoalkylindole, eicosanoid, and other structures) in an effort to define the requirements for high-affinity association and efficacy, such that pharmacologically distinct agonists and antagonist (CB1- or CB2-selective) can be determined or developed. This project involves close collaboration with synthetic, analytical, and computational chemist. "Cannabinoid Receptors in Neuronal Cells and Brain" addresses the mechanisms through which the receptor signals its response through G proteins, and the mechanisms whereby the cell regulates this activity through modification of the receptor (e.g., phosphorylation, palmitoylation) and regulation of synthesis, cellular localization, and degradation.